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在mpkCCD细胞中,Epac诱导了赖诺丁受体依赖的细胞内和器官间动员
Kay-Pong Yip1,2, Luisa Ribeiro-Silva1, Byeong Cha1
1Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
氨酸血管压素 (AVP) 在脏收集管道中的信号传输涉及 (Ca2+) 振荡,由Epac. 这项研究揭示了Epac诱导的Ca2+转移在细胞中的内分泌网膜和线粒体之间.
科学领域:
- 细胞和分子生理学细胞和分子生理学
- 脏生理学 脏生理学
- 信号传递 信号传递
背景情况:
- 氨酸血管压素 (AVP) 触发动性细胞内 ([Ca2+]i) 在脏收集管道中的增加,这对角外细胞形成至关重要.
- 这种由AVP诱导的动员是由循环腺单酸盐 (Epac) 直接激活的交换蛋白介导的.
- 鼠主要脏皮层收集管 (mpkCCD) 细胞是研究脏中AVP信号的模型.
研究的目的:
- 为了描述mpkCCD细胞中的动员.
- 通过使用mpkCCD细胞研究Epac诱导的细胞内和器官内动员.
- 阐明Epac在调节细胞质,内质网膜 (ER) 和线粒体内的动态中的作用.
主要方法:
- 使用的mpkCCD细胞和隔离的透的内髓收集管道.
- 采用了对Ca2+敏感的光探头和特定位置的生物传感器来监测细胞质,ER光和线粒体基质中的Ca2+.
- 进行了共聚焦显微镜以捕获光图像,并评估了氨酸受体 (RyR) 和异醇1,4,5三酸盐受体 (IP3R) 连接体,以及Epac特定的cAMP模拟物 (Me-cAMP/AM) 的作用.
主要成果:
- mpkCCD细胞在刺激RyRs和IP3Rs时表现出Ca2+动员和振荡,类似于隔离的内髓收集管道.
- 特定于Epac的激动剂Me-cAMP/AM诱导了强大的Ca2+动员和振荡,导致Ca2+从ER释放并转移到线粒体中.
- Epac的激活导致了细胞质和线粒体中同步的Ca2+峰值,耗尽了ER Ca2+储存,并触发了储存运行的Ca2+进入 (SOCE).
结论:
- mpkCCD细胞准确地模拟了孤立脏收集管道的Ca2+调动特征.
- Epac激活驱动RyR-依赖的Ca2+信号传递和ER-线粒体Ca2+传输,与IP3R激活不同.
- 在mpkCCD细胞中的ER-线粒体Ca2+合提供了一个模型来研究线粒体调节细胞质Ca2+信号和管功能.
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